Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling
Osteoporosis is characterized by a decrease in bone mass and destruction of the bone microarchitecture, and it commonly occurs in postmenopausal women and the elderly. Overactivation of osteoclasts caused by the inflammatory response or oxidative stress leads to osteoporosis. An increasing number of...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/9f7d8149ba67406f8401abd0d475ae73 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:9f7d8149ba67406f8401abd0d475ae73 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:9f7d8149ba67406f8401abd0d475ae732021-12-01T07:40:15ZAzilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling1663-981210.3389/fphar.2021.774709https://doaj.org/article/9f7d8149ba67406f8401abd0d475ae732021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.774709/fullhttps://doaj.org/toc/1663-9812Osteoporosis is characterized by a decrease in bone mass and destruction of the bone microarchitecture, and it commonly occurs in postmenopausal women and the elderly. Overactivation of osteoclasts caused by the inflammatory response or oxidative stress leads to osteoporosis. An increasing number of studies have suggested that intracellular reactive oxygen species (ROS) are strongly associated with osteoclastogenesis. As a novel angiotensin (Ang) II receptor blocker (ARB), azilsartan was reported to be associated with the inhibition of intracellular oxidative stress processes. However, the relationship between azilsartan and osteoclastogenesis is still unknown. In this study, we explored the effect of azilsartan on ovariectomy-induced osteoporosis in mice. Azilsartan significantly inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis and downregulated the expression of osteoclast-associated markers (Nfatc1, c-Fos, and Ctsk) in vitro. Furthermore, azilsartan reduced RANKL-induced ROS production by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Mechanistically, azilsartan inhibited the activation of MAPK/NF-κB signaling pathways, while Nrf2 silencing reversed the inhibitory effect of azilsartan on MAPK/NF-κB signaling pathways. Consistent with the in vitro data, azilsartan administration ameliorated ovariectomy (OVX)-induced osteoporosis, and decreased ROS levels in vivo. In conclusion, azilsartan inhibited oxidative stress and may be a novel treatment strategy for osteoporosis caused by osteoclast overactivation.Bin PanBin PanBin PanLin ZhengLin ZhengJiawei FangJiawei FangYe LinYe LinHehuan LaiJiawei GaoJiawei GaoJiawei GaoWenzheng PanWenzheng PanYejin ZhangYejin ZhangYejin ZhangKainan NiKainan NiChao LouChao LouDengwei HeDengwei HeFrontiers Media S.A.articleosteoporosisreactive oxygen speciesNrf2osteoclastazilsartanTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
osteoporosis reactive oxygen species Nrf2 osteoclast azilsartan Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
osteoporosis reactive oxygen species Nrf2 osteoclast azilsartan Therapeutics. Pharmacology RM1-950 Bin Pan Bin Pan Bin Pan Lin Zheng Lin Zheng Jiawei Fang Jiawei Fang Ye Lin Ye Lin Hehuan Lai Jiawei Gao Jiawei Gao Jiawei Gao Wenzheng Pan Wenzheng Pan Yejin Zhang Yejin Zhang Yejin Zhang Kainan Ni Kainan Ni Chao Lou Chao Lou Dengwei He Dengwei He Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling |
| description |
Osteoporosis is characterized by a decrease in bone mass and destruction of the bone microarchitecture, and it commonly occurs in postmenopausal women and the elderly. Overactivation of osteoclasts caused by the inflammatory response or oxidative stress leads to osteoporosis. An increasing number of studies have suggested that intracellular reactive oxygen species (ROS) are strongly associated with osteoclastogenesis. As a novel angiotensin (Ang) II receptor blocker (ARB), azilsartan was reported to be associated with the inhibition of intracellular oxidative stress processes. However, the relationship between azilsartan and osteoclastogenesis is still unknown. In this study, we explored the effect of azilsartan on ovariectomy-induced osteoporosis in mice. Azilsartan significantly inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis and downregulated the expression of osteoclast-associated markers (Nfatc1, c-Fos, and Ctsk) in vitro. Furthermore, azilsartan reduced RANKL-induced ROS production by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Mechanistically, azilsartan inhibited the activation of MAPK/NF-κB signaling pathways, while Nrf2 silencing reversed the inhibitory effect of azilsartan on MAPK/NF-κB signaling pathways. Consistent with the in vitro data, azilsartan administration ameliorated ovariectomy (OVX)-induced osteoporosis, and decreased ROS levels in vivo. In conclusion, azilsartan inhibited oxidative stress and may be a novel treatment strategy for osteoporosis caused by osteoclast overactivation. |
| format |
article |
| author |
Bin Pan Bin Pan Bin Pan Lin Zheng Lin Zheng Jiawei Fang Jiawei Fang Ye Lin Ye Lin Hehuan Lai Jiawei Gao Jiawei Gao Jiawei Gao Wenzheng Pan Wenzheng Pan Yejin Zhang Yejin Zhang Yejin Zhang Kainan Ni Kainan Ni Chao Lou Chao Lou Dengwei He Dengwei He |
| author_facet |
Bin Pan Bin Pan Bin Pan Lin Zheng Lin Zheng Jiawei Fang Jiawei Fang Ye Lin Ye Lin Hehuan Lai Jiawei Gao Jiawei Gao Jiawei Gao Wenzheng Pan Wenzheng Pan Yejin Zhang Yejin Zhang Yejin Zhang Kainan Ni Kainan Ni Chao Lou Chao Lou Dengwei He Dengwei He |
| author_sort |
Bin Pan |
| title |
Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling |
| title_short |
Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling |
| title_full |
Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling |
| title_fullStr |
Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling |
| title_full_unstemmed |
Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling |
| title_sort |
azilsartan suppresses osteoclastogenesis and ameliorates ovariectomy-induced osteoporosis by inhibiting reactive oxygen species production and activating nrf2 signaling |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/9f7d8149ba67406f8401abd0d475ae73 |
| work_keys_str_mv |
AT binpan azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT binpan azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT binpan azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT linzheng azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT linzheng azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT jiaweifang azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT jiaweifang azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT yelin azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT yelin azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT hehuanlai azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT jiaweigao azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT jiaweigao azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT jiaweigao azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT wenzhengpan azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT wenzhengpan azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT yejinzhang azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT yejinzhang azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT yejinzhang azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT kainanni azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT kainanni azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT chaolou azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT chaolou azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT dengweihe azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling AT dengweihe azilsartansuppressesosteoclastogenesisandamelioratesovariectomyinducedosteoporosisbyinhibitingreactiveoxygenspeciesproductionandactivatingnrf2signaling |
| _version_ |
1718405430091186176 |